Our previous studies have demonstrated that varying fMRI paradigms may be used as probes of different aspects of language processing and that visual analysis is equivalent to quantitative region of interest analysis. [unreadable] [unreadable] [unreadable] fMRI language tasks reliably identify language areas in children and adults with localization related epilepsy Objective: To determine the relationship between structural lesions and atypical language representation in patients with left hemisphere epileptogenic zones. We studied 102 patients (mean age 22; range 4-55 years), using whole brain fMRI (EPI BOLD) with three language tasks using a block design: Verbal Fluency; Reading Comprehension, and Auditory Comprehension. fMRI t maps were rated visually. Results: fMRI showed left language dominance in 72 patients. Atypical language was found in 30 patients (29%). The incidence of atypical language varied with MRI type. Every patient (6/6) with a history of stroke, 36% (13/ 36) with normal MRI, 21% (6 /29) with mesial temporal sclerosis, 14% (4 /28) with focal cortical lesions (dysplasia, tumor, vascular malformation), and 33% (1/3) with Rasmussen.s Encephalitis had atypical language. Atypical language was more prevalent in patients with early seizure onset (43.2%, p< .05) and atypical handedness. Multivariate logistic regression analysis revealed that three clinical factors, handedness, seizure onset, and MRI type, accounted for a significant amount of the variance in language activation patterns. Early seizure onset was the strongest factor, followed by handedness. None of the three clinical factors were correlated with each other (p> .40). Patients with atypical language had lower verbal abilities (F = 6.96, p = .01) and a trend towards lower nonverbal abilities. Among patients with left hemisphere foci, fMRI language activation paradigms show atypical language in one third of patients with non lesional epilepsy, and one fifth of patients with MTS, but only one eighth of patients with small, discreet lesions. Early destructive processes involving substantial left hemisphere regions are most likely to lead to language re-organization. Early seizure onset, and atypical handedness, as well as the location and nature of pathological substrate, are important factors in language reorganization. It is uncertain if lesion size or location is more important. [unreadable] [unreadable] fMRI language tasks reliably identify language areas but memory paradigms have been problematic. We examined an auditory description decision task for hippocampal activation and compared it to the intracarotid amytal test (IAT) in 25 patients using a hippocampal mask analysis. We found that activation in hippocampus mostly reflected language dominance except where the hippocampus was sclerotic. We found poor correlation with IAT laterality indices, and only fair correlation between dominant HF activation and IAT memory capacity based on IAT. [unreadable] [unreadable] We used the paradigm of repetition priming to study the effects of epilepsy on memory. Repetition priming is characterized by improved identification of a stimulus following a previous encounter with that stimulus. This phenomenon has been linked to a decreased neuronal response commonly referred to as repetition suppression (RS). Recent evidence suggests that repetition priming may be mediated via interactions between frontal and posterior cortices. RS in posterior regions may be mediated by feedback from more anterior regions of the object processing stream. However, whether anterior temporal regions play a role in mediating RS in posterior cortices has not been evaluated. To address this question we are studying object repetition priming in patients with temporal lobe epilepsy before and after anterior temporal lobectomy. In three patients who had left temporal epileptic foci, subjects named pictures of common objects presented in a rapid event-related design. Prior to scanning subjects named 96 objects. During scanning, subjects silently named the same items (Repeated) intermixed with 96 objects not previously seen (Novel). Subjects indicated successful covert naming via a button press. The task was repeated 6-18 months following therapeutic anterior temporal lobectomy in an identical fashion but using different stimuli. [unreadable] All three patients were highly accurate at object naming both pre- and post-operatively. In addition, robust priming, as measured by button-push in the scanner, was seen pre-operatively (available for two subject), but not post-operatively (available for one subject). Most important, whereas all three patients showed robust RS bilaterally in posterior temporal and occipital cortices prior to surgery, RS was eliminated after surgery. These results suggest that RS in posterior cortices is dependent on feedback from more anterior regions of the temporal lobes. It remains to be determined whether the effect is due directly to the removal of left anterior temporal structures, or results from a disconnection of information from left inferior frontal cortex to posterior temporal regions.[unreadable] [unreadable] Autosomal Dominant Partial Epilepsy with Auditory Features (ADPEAF), is caused by mutations in the LG1 gene, believed to be involved in neuronal migration. Ictal events include auditory phenomena, such as formed or unformed sounds, distortions, and sensory aphasia, and complex partial and secondary generalized tonic-clonic seizures, suggesting dominant temporal lobe pathology. We used functional magnetic resonance imaging to investigate auditory and verbal processing in patients with ADPEAF, unaffected family members, and unrelated controls. All subjects were right-handed. Each subject had 3D fast SPGR anatomical images. Monitored activation paradigms included an auditory description decision task (ASDDT), and a rising/falling musical tone discrimination task. Control conditions were reverse speech for auditory description decision, and silent rest for tone discrimination. Images were realigned, normalized, smoothed to 8 mm and analyzed with SPM2. Results were examined at p<0.05 corrected for multiple comparisons, and at p< 0.001 uncorrected. The results showed that controls showed bilateral fronto-temporal activation during tone discrimination, and predominantly left temporal and inferior frontal activation on ASDDT. Patients had decreased activation compared to normal controls on both tasks, although the effect was more marked on the semantic description decision task, where normal left posterior temporal activation was not seen, even at reduced statistical thresholds. In individual patients, activation was reduced, or displaced from control localizations. Structural MRI showed no abnormalities. Patients seizures were well-controlled on a variety of antiepileptic drugs (AEDs). Thus, our data suggest that patients with ADPEAF have disturbed functional anatomy for auditory processing. Possible AED effects cannot be excluded, but are not seen in other TLE populations. However, the LGI1 mutation may lead to cortical dysfunction in the absence of structural changes. [unreadable] [unreadable] Overall, our studies show the complex interaction of structural and functional deficts in people with epilepsy. Clinically, they highlight the need for careful individual functional mapping.